AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

Objective To investigate the relationship between initial serum testosterone level and aggressive characteristics,progression and prognosis of metastatic prostate cancer(mPCa).Methods The clinical data of 302 mPCa patients diagnosed with biopsy and auxiliary examinations at the First Affiliated Hospital of Xinjiang Medical University during Aug.2010 and Aug.2022 were retrospectively analyzed,including 148 cases in the serum testosterone low level group(≤12 nmol/L)and 154 in the normal level group(＞12 nmol/L).The independent risk factors associated with aggressive features were analyzed with multifactorial logistic regression,survival was determined with Kaplan-Meier method,the independent risk factors affecting progression and prognosis were identified with multifactorial Cox regression modeling,and the value of initial serum testosterone level in predicting the progression and survival was assessed with receiver operating characteristic(ROC)curve.Results The low level group had a higher proportion of Gleason score ≥8,T stage＞3,initial prostate-specific antigen(PSA)＞200 ng/mL,high tumor load,visceral metastasis,PSA≥ 0.2 ng/mL after 6 months of treatment,and higher body mass index(BMI),but the PSA decline rate after 6 months of treatment was lower than that in the normal level group(P＜0.05).Multifactorial logistic regression showed that initial serum testosterone level＞12 nmol/L was a protective factor for high tumor load(OR=0.137,95％CI:0.070-0.265,P＜0.001),Gleason score ≥8(OR=0.371,95％CI:0.184-0.750,P=0.006)and visceral metastasis(OR=0.337,95％CI:0.175-0.652,P=0.001).The median progression-free survival was shorter in the low level group than in the normal level group(15 months vs.20 months,P＜0.001),and the median overall survival time was also shorter(45 months vs.86 months,P＜0.001).Multifactorial Cox regression analysis showed that Gleason score ≥8,high tumor load,PSA value at 6 months of treatment,and PSA decline rate were independent influencing factors for progression to castration resistant prostate cancer(CRPC)(P＜0.05).The risk of death in patients with high tumor load was 2.510 times higher than that of patients with low tumor load(95％CI:1.555-4.051,P＜0.001).ROC curves showed that initial serum testosterone level could predict the risk of progression to CRPC(AUC:0.645)and survival(AUC:0.595).Conclusion Low level initial serum testosterone is associated with an aggressive profile and poor prognosis of mPCa,and can predict the risk of progression and survival status of mPCa patients.

Objective To explore the correlation between daunorubicin(DNR)resistance and expression of pro-grammed death receptor ligand 1(PD-L1)in children with acute myeloid leukemia(AML).Methods Totally 110 bone marrow samples were selected from AML patients admitted to Zhengzhou University Affiliated Children's Hos-pital from January 2016 to December 2022 as the study group,50 bone marrow samples from normal bone marrow donors were used as the control group.Human AML cell lines HL60,THP-1,U-937,and Molm-13 were cultured,and the expression of PD-L1 protein was detected by Western blot.LV-PD-L1-shRNA and LV-PD-L1-WT-OE lenti-viral vectors were constructed.The effect and mechanism of PD-L1 on DNR resistance in Molm-13 cells were ana-lyzed.Results The expression level of PD-L1 protein was higher than that in control group and the expression level of PD-L1 protein in AMI cell lines was higher than that in healthy bone marrow mononuclear cells(BMMC)(P＜0.05).PD-L1 expression was related to white blood cell count,bone marrow primitive cell ratio,prognostic risk stratification and disease remission after two standard chemotherapy regimens in AML patients(P＜0.05).The overall survival rate of the PD-L1 high expression group was lower than that of the PD-L1 low expression group(P＜0.05).Compared with the LV-PD-L1-WT-OE group,the LV-PD-L1-shRNA group showed a decrease in PD-L1 mRNA expression,cell proliferation activity but an increased apoptosis rate(P＜0.05).LV-PD-L1-shRNA enhanced sensitivity of Molm-13 cells to DNR.TCGA database analysis showed that glucose 6-phosphate dehydro-genase(G6PD)was a potential target gene for PD-L1.Conclusions The high expression of PD-L1 in pediatric AML is related to chemotherapy resistance in children with AML,and DNR resistance might be caused through reg-ulation of G6PD.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective:To analyze the metabolic mechanism of papillary thyroid cancer(PTC) in normal and Hashimoto′s thyroiditis(HT) background, and to explore the relationship between HT and PTC.Methods:This study included a matched sample set collected from Tianjin Medical University General Hospital between January 2018 and January 2019, consisting of PTC and paracancular tissue from 31 cases with coexisting HT(HT group), and 30 cases without(NC group), all confirmed pathologically following thyroidectomy. The ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to acquire data from the samples. Metabolite differences between the two groups were compared, aiming to identify distinct metabolic mechanisms of PTC under different backgrounds. Metabolic pathway analysis was conducted using Metabo-Analyst 5.0 to explore relevant metabolic pathways.Results:The HT group and NC group shared 7 common differentially expressed metabolites, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil, and taurine. Logistic regression model combined with receiver operating characteristic(ROC) analysis of these 7 biomarkers yielded excellent discriminatory capacity for PTC(area under ROC curve of HT group and NC group were 0.867 and 0.973, respectively). The common metabolic pathways were taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartic acid and glutamic acid metabolism, arginine and proline metabolism, and glutamine and glutamic acid metabolism. The specific metabolic pathways in HT group were aminoacyl tRNA biosynthesis, glycine, serine, and threonine metabolism.Conclusion:The metabolic profiles of thyroid cancer exhibit significant differences between cases with normal backgrounds and those with HT. The specific pathways for PTC and HT are aminoacyl tRNA biosynthesis and the metabolism of glycine, serine, and threonine.

Humans ; Female ; Breast Neoplasms/genetics* ; Prognosis ; Gene Expression Profiling ; Biomarkers, Tumor/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Receptor, ErbB-2/metabolism* ; Gene Regulatory Networks/genetics*

Objective:To learn about the changes of the condition of coal-burning-borne endemic arsenism, the use of improved stoves and the formation of health-related behaviors in Shaanxi Province, and evaluate the effect of prevention and control measures.Methods:From 2015 to 2020, according to the "Implementation Plan for Monitoring Coal-burning-borne Endemic Arsenism in Shaanxi Province", regular field surveys were carried out in 4 natural villages, 2 counties in Ankang City and Hanzhong City, Shaanxi Province, to learn about the basic prevention and control situation in the monitoring village. Using the simple random sampling method, 10 families in each village were selected to investigate the use of stoves and the formation of health-related behaviors, and 5 of these families were selected to collect coal samples for arsenic content determination in accordance with the "Determination of Arsenic in Coal" (GB/T 3058-2008). According to the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015), the condition of the people exposed to high arsenic coal in the monitoring village was investigated. Urine samples of 30 adult patients (half males and half females) with arsenic poisoning were collected, the content of arsenic in urine was determined by the "Urine-Determination of Arsenic-Silver Diethyldithiocarbamate-Triethanolamine-Spectrophotometric Method" (WS/T 28-1996).Results:A total of 240 households were monitored in the past 6 years, and the quality conformance and correct utilization rates of improved stoves in the households monitored in the disease areas remained at 100.00% in 2018 - 2020. The utilization rate of clean energy increased from 75.00% (30/40) in 2015 to 100.00% (40/40) in 2018 - 2020 (χ 2trend = 25.5, P < 0.001). The 73.75% (177/240) of households using a variety of clean energy. From 2018 to 2020, the correct drying, storage and pre-processing washing rates of corn and pepper continued to reach 100.00% (40/40). The arsenic content of coal ( n = 120) in the disease areas was (118.09 ± 57.91) mg/kg, ranging from 16.70 to 280.94 mg/kg. The detection rate of arsenic poisoning decreased from 6.34% (231/3 646) in 2015 to 2.90% (109/3 754) in 2020 (χ 2trend = 121.8, P < 0.001), and no skin cancer or Bowen's disease was detected. The geometric mean of arsenic content in urine ( n = 720) was 0.038 1 mg/L, ranging from 0.000 5 to 0.312 9 mg/L. Conclusions:The condition of coal-burning-borne endemic arsenism areas in Shaanxi Province has reached the national elimination standard. The quality and correct utilization rate of improved stoves and the rate of using clean energy have increased. The healthy-related behaviors the people in the endemic areas have been basically formed. The prevention and control work has achieved good results.

Objective:To explore the effects of myosteatosis and blood glucose (BG) on postoperative complications in non-diabetic gastric cancer patients receiving supplemental parenteral nutrition (SPN) after gastrectomy.Methods:Patients who underwent radical gastrectomy between March 2017 and June 2021 in the Department of Surgical Oncology, the First Hospital of Lanzhou University were included in this study. Various preoperative inflammatory and nutritional indicators, including skeletal muscle metrics at the third lumbar level on CT, were collected retrospectively. Postoperative BG within 3 days and complications within 30 days were monitored. Patients were divided into two groups according to the presence or absence of myosteatosis (assessed via skeletal muscle density [SMD]) and the differences in postoperative BG and complication incidence were compared. Mediation model was used to analyze the mediating effect of BG in the association between SMD and postoperative complications.Results:A total of 357 patients were included in the study. Compared with the 299(83.8%) patients without myosteatosis , the incidence of hyperglycemia, mean BG, maximal BG, and BG fluctuation while on SPN in the 58(16.2%) patients with myosteatosis were higher, and the comprehensive complication index (CCI) and the incidence of complication were higher ( P<0.05). More importantly, BG showed the mediation effect of -0.0892 in the effect of SMD on CCI ( P<0.05), with the effect size of 19.3％. Conclusion:Myosteatosis and postoperative hyperglycemia are associated with higher incidence of complications, and BG plays an intermediary role in the association between myosteatosis and CCI.

Objective:To investigate the application value of right-hand rule in determining left-right axis and fetal situs in prenatal MRI.Methods:The prenatal MRI data of 254 fetuses were included retrospectively in West China Second University Hospital, Sichuan University from December 2017 to February 2021, which were followed by clear postpartum diagnosis. Fetal left-right axis and situs (orientation of gastric vacuole, liver and heart) were determined by the same radiologist blindly using general experience and right-hand rule respectively, meanwhile, results and time of each case were recorded. The right-hand rule was described in detail below: use your right hand to make a fist, and with thumb outstretched; the fetal head was represented by your right fist, the forearm represented the fetal body, the dorsal side of your fist represented the fetal occiput and spine column, the palm side represented the fetal belly, and your four fingers represented the fetal face, then the left side of fetus was exactly the direction your thumb pointing to. The postpartum imaging was used as the gold standard for situs anomalies. The time to determine the fetal left-right axis was compared using paired t test for statistical analysis. Results:Four fetuses were found situs anomalies in postpartum imaging. There were 1 missed case and 1 misdiagnosed case when using general experience to determine fetal situs, neither missed case nor misdiagnosis were present when using right-hand rule. The average time of using general experience or right-hand rule to determine the fetal left-right axis and situs were (35±6)s and (24±9)s respectively, and the difference was statistically significant ( t=20.65, P<0.001). Conclusions:The right-hand rule is an accurate and efficient method for determining left-right axis and situs in prenatal MRI, which can effectively reduce missed diagnosis and misdiagnosis of situs anomalies, especially in situs inversus totalis.

OBJECTIVE：To study the sta bility，in vivo release characteristics and tissue distribution of docetaxel （DTX）- dihydroartemisinin（DHA）conjugated prodrug self-assembled nanoparticles （DTX-S-S-DHA NPs ）. METHODS ：HPLC method was adopted to analyze DTX-S-S-DHA in vitro . The phycial and long-term stability of DTX-S-S-DHA NPs in mediums [water ， saline，phosphate buffer （PBS，pH 7.4）and RPMI 1640 medium] were investigated by using particle size ，polydispersity index （PDI）and encapsulation efficiency （EE）as evaluation indexes. The in vitro release characteristics of DTX-S-S-DHA released from DTX-S-S-DHA NPs was also investigated with small glass method ，using 30％ ethanol solution with or without 10 mmol/L dithiothreitol（DTT）as medium. The small live animal imager was adopted to investigate the tissue distribution and tumor targeting capability of DiR-labeled DTX-S-S-DHA NPs （DTX-S-S-DHA/DiR NPs ）in breast cancer bearing mice. RESULTS ：In stability test，there was no statistical difference in particle size ，PDI and EE of DTX-S-S-DHA NPs incubated in water ，normal saline ，PBS and RPMI 1640 medium for 24 h. When stored at 4 ℃，with the increase of storage time ，the particle size of DTX-S-S-DHA NPs in normal saline gradually increased ，while those in PBS gradually decreased ；EE of both gradually decreased to less than 75％， but there was no significant change in particle size ，PDI and EE of DTX-S-S-DHA NPs in water and RPMI 1640 medium. In the in vitro release experiments ，DTX-S-S-DHA in DTX-S-S-DHA NPs was not released in the release medium containing 10 mmol/L DTT；at 24 h，the cumulative release rate of DTX-S-S-DHA released from DTX-S-S-DHA NPs in release medium without DTT was about 83％，which was in line with first-order kinetic model. In tissue distribution test ，the distribution of DTX-S-S-DHA/DiR NPs in tumor sites of mice was significantly more than in other tissues （heart，liver，spleen，lung and kidney ）. CONCLUSIONS ： DTX-S-S-DHA NPs show good physical stability in different mediums ，especially have good long-term stability in water and RPMI ； 1640 medium；they can quickly release the parent drug in the reduction environment and has good tumor targeting.